MDR-TB Patients Research Articles

Bedaquiline-Based Short Course Regime for MDR-TB -“The Indian Scenario”

India ranks highest in number of Tuberculosis (TB) and Multi Drug Resistant (MDR) TB patients globally (World Health Organization. Global tuberculosis report (2018). Maximum number of deaths due to TB also occur in India. A short course regime for treating Fluroquinolone (FQ) Sensitive MDR TB has been recommended by the World Health Organization (WHO) in 2020 with a duration of 9-11 months. India has also adopted the BDQ Short course regime for MDR-TB patients with multiple exclusion criteria. The excluded patients would receive a longer BDQ based regime which may last 18-20 months. The purpose of this mini-review is to emphasize the possibilities of high failure rates in the BDQ based short course regime, especially in the Context of India due to high baseline FQ resistance and an acute shortage of Drug Sensitivity Tests (DST) tests especially for FQ. Moreover, the need of High dose Isoniazid (Hh ) in the regime may be only a toxic addition in about 80% of patients leading to adverse effects, some of which may be fatal. Failure of BDQ-based short course regime would lead to a catastrophic amplification of the resistance of critically essential drugs such as BDQ and Clofazimine (CFZ). Chances of cure in such patients with Extensively Drug Resistant (XDR) TB would be slim, if not altogether absent.

Quality of Life Amongst Multidrug-Resistant TB Patients: An Exploratory Study About Distributive Dimensions and Interactions.

Background: Multidrug-resistant (MDR)-TB has emerged as a major challenge to eliminate TB as envisioned at policy level. Distinctive traits associated with the disease such as physical, psychosocial and environmental dimensions may influence the treatment outcome in both directions. Quality of life (QoL) indicators may capture these traits distinctively.Objective: To quantify the differential effect of MDR-TB on specific QoL domains, their distributions across the strata and to check for possible interactions.Method: This community-based cross-sectional study was conducted on 98 MDR-TB patients registered in the calendar year 2017 under National Tuberculosis Elimination Programme (NTEP) in a central Indian district using the WHO-QoL BREF Scale by patients in their vicinity. The transformed domain scores were descriptively summarized, stratified and exploratory visualised. Likert mapping for each item was done. A two-way ANOVA test was applied to check differences across strata and interaction effects were calculated.Result: Participants perceived a higher QoL in the social domain (median score 69, IQR 56-75) while the psychological health domain (median 31 IQR 20.5-44) was professed as most negotiated by disease. More than 50% of participants were found to be dissatisfied with their assumed physical status in item-wise analysis. A statistically significant interaction (p=0.008) was detected with education strata to income tertile most evident in the physical domain while psychological domain alone (p=0.017) without significant interaction with treatment duration (p=0.316) was associated with the type of TB. Overall QoL scores were tilted in favour of an urban setting, male gender and towards a relatively younger population.Conclusion: The overall deficits in QoL are evident in the study, per se in the psychological and physical domains. Moreover there is an inequitable distribution of these scores as revealed in the study. Inclusion of an additional parameter of periodical QoL assessment may thus predict the outcome at individual level and may address this inequity at policy level.

Recognition of specific immunogenic antigens with potential diagnostic value in multi-drug resistant Mycobacterium tuberculosis inducing humoral immunity in MDR-TB patients.

Tuberculosis (TB) as a public health crisis is caused by the intracellular bacterium Mycobacterium tuberculosis. Detection of immunogenic proteins in TB is valuable for the development of diagnostic tests, vaccine formulations and monitoring treatment outcome. In this study, we differentiated the immune-reactivity of proteins in multidrug-resistant tuberculosis (MDRTB) and drug-susceptible strains using purified anti-MDRTB antibodies isolated from inpatients. Our data showed that the anti- MDRTB antibody was well able to detect the MDR strain in the patient's sputum. The immunogenic proteins of MDRTB were purified by affinity chromatography and subjected to matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Analysis of the data revealed that seven MDRTB immunogenic proteins, including Rv2986c (HupB), Rv3699, Rv1133c (MetE), Rv0440 (GroEL), Rv3057c, Rv2558 and Rv2971 are involved in DNA stability, metabolism, cellular processes and some unknown functions. Similarities in the electrophoresis protein profiles were evident between the extracts of MDR and sensitive TB strains. However, the protein expression patterns of MDRTB isolates were distinguishable from that formed by susceptible TB strains.

Studi Farmakovigilans Pengobatan MDR-TB pada Pasien Rawat Jalan di RSUD Embung Fatimah Kota Batam Tahun 2020

Pharmacovigilance is a science related to collecting, detecting, monitoring, assessing, and preventing side effects of pharmaceutical products. The design of this research is retrospectively descriptive. To understand the characteristics of MDR-TB patients and the side effects of the drug that MDR-TB patients feel. The research was conducted between January 2020 – June 2020. The research was conducted at Embung Fatimah Hospital. The number of confirmed patients with MDR TB was 24 patients, 9 male (37.5%) and 15 women (62.5%); the average MDR-TB patient aged 26-45 years (54.20%), Batu Aji (45.83%) be the place most exposed to MDR-TB with a social history of smoking, drugs, and alcohol. The results showed patients who experienced 41.7% anorexia side effects, 100% nausea, 100% vomiting, reduced appetite by 37.5%, 79.2% pain at the injection site, 79.2% joint pain, 58.3% reduced hearing and 25% vertigo. In conclusion, most side effects are nausea and vomiting.

Pre-extensively drug-resistant tuberculosis among multidrug-resistant tuberculosis patients in Ethiopia: a laboratory-based surveillance study

BackgroundThe rise of drug-resistant tuberculosis (DR-TB) has presented a substantial challenge to the national tuberculosis (TB) control program. Understanding the epidemiology of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) could help clinicians to adapt MDR-TB treatment regimens at an earlier stage. This study aimed to assess second-line anti-TB drug resistance among MDR-TB patients in Ethiopia using routine laboratory-based data. MethodsLaboratory-based cross-sectional data were collected from the national TB reference laboratory and seven regional tuberculosis culture laboratories in Ethiopia from July 2019 to March 2022. The required data, such as drug-susceptibility testing (DST) results and sociodemographics, were collected on a structured checklist from laboratory registration books and electronic databases. Data were entered into a Microsoft Excel spreadsheet and analyzed using SPSS version 23. Descriptive statistics were performed to show the distribution and magnitude of drug resistance. ResultsSecond-line drugs (SLDs) susceptibility testing was performed for 644 MDR isolates, of which 19 (3%) were found to be pre-XDR-TB cases. Of the total MDR-TB isolates, 19 (3%) were resistant to at least one fluoroquinolone drug, while 11 (1.7%) were resistant to at least one injectable second-line drug. Of the 644 MDR-TB isolates, 1.9% (5/261) pre-XDR were from new MDR-TB cases, while 3.7% (14/383) were from previously treated MDR-TB patients. The most frequently identified mutations, based on MTBDRsl results, were in codon A90V of the gyrA gene (77.3%) and A1401G of the rrs gene (45.5%). ConclusionThe overall prevalence of pre-XDR-TB in Ethiopia is considerable. The majority of SLD resistance mutations were in the gyrA gene at position A90V. Modern, rapid DST is necessary to enable identification of pre-XDR-TB and XDR-TB in supporting proper regimen administration for patients.

Development and validation of a nomogram for the prediction of late culture conversion among multi-drug resistant tuberculosis patients in North West Ethiopia: An application of prediction modelling.

Multi-drug resistant tuberculosis has impeded tuberculosis prevention and control due to its low treatment efficiency and prolonged infectious periods. Early culture conversion status has long been used as a predictor of good treatment outcomes and an important infection control metric, as culture-negative patients are less likely to spread tuberculosis. There is also evidence that suggests that delayed sputum conversion is linked to negative outcomes. Therefore, this study was aimed at developing a nomogram to predict the risk of late culture conversion in patients with multi-drug resistant tuberculosis using readily available predictors. The objective of this study was to develop and validate a risk prediction nomogram for the prediction of late culture conversion among multi-drug resistant tuberculosis patients in North-West Ethiopia. Multi-drug resistant tuberculosis data from the University of Gondar and the Debre Markos referral hospitals have been used and a total of 316 patients were involved. The analysis was carried out using STATA version 16 and R version 4.0.5 statistical software. Based on the binomial logistic regression model, a validated simplified risk prediction model (nomogram) was built, and its performance was evaluated by assessing its discriminatory power and calibration. Finally, decision curve analysis (DCA) was used to assess the generated model's clinical and public health impact. Registration group, HIV co-infection, baseline BMI, baseline sputum smear grade, and radiological abnormalities were prognostic determinants used in the construction of the nomogram. The model has a discriminating power of 0.725 (95% CI: 0.669, 0.781) and a P-value of 0.665 in the calibration test. It was internally validated using the bootstrapping method, and it was found to perform similarly to the model developed on the entire dataset. The decision curve analysis revealed that the model has better clinical and public health impact than other strategies specified. The developed nomogram, which has a satisfactory level of accuracy and good calibration, can be utilized to predict late culture conversion in MDR-TB patients. The model has been found to be useful in clinical practice and is clinically interpretable.

A RETROSPECTIVE STUDY OF ADVERSE DRUG REACTION IN MULTIDRUG-RESISTANT TUBERCULOSIS PATIENTS AT TERTIARY CARE HOSPITAL

Objective: The objective of the study was to the analysis of different parameters including admission type, demographics, type of reaction, the seriousness of reaction, classification of organ system, drugs involved, action taken and outcome of reactions, causality assessment, severity assessment, and the preventability of ADRs for multidrug-resistant tuberculosis patients. Methods: This retrospective observational study was conducted during the period of September 2017 to June 2020 (34 months) at ADR Monitoring Centre, Department of Pharmacology, Jawaharlal Nehru Medical College, Ajmer, Rajasthan. All spontaneously reported ADRs were evaluated using various parameters such as type of reaction, causality assessment, preventability, and severity. Results: In the present study, 92 (9.29%) ADRs were reported in relation to 68 MDR-TB patients. The majority of ADRs were considered probable (73.92%), moderate (41.30%), and definitely preventable (42.39%) in nature. In our study, most of the suspected drug names were included: 23 (25%) pyrazinamide, followed by 22 (23.91%) kanamycin, 12 (13.04%) cycloserine, and 11 (11.96%) linezolid. The majority of ADRs were non-serious (67.39%) in nature. ADRs were most commonly reported, with 17 (18.48%) reporting ototoxicity and 17 (18.48%) reporting joint pain, followed by 4 (4.35%) reporting burning feet syndrome, 4 (4.35%) reporting generalized itching, and 4 (4.35%) reporting psychosis. Conclusion: Our study included 36 different types of suspected ADRs that were reported with multiple frequencies due to 16 categories of drugs and combinations of drugs. The majority of patients were recovering and recovered from concerns associated with ADR after necessary medical intervention and management. Our purpose is to rationale the use of medicines for drug safety as well as patient safety.

Mapping of antibiotic resistance in Multi-Drug Resistance Tuberculosis at RSUD Arifin Achmad, Riau Province

Tuberculosis is a disease caused by the bacteria Mycobacterium tuberculosis. Resistance is a condition where an antibiotic is not able to kill Mycobacterium tuberculosis. The type of research used is descriptive with a mixed-method approach. It was found that most MDR-TB patients were male (67.2%), aged 41-50 years (26.9%), and lived in Pekanbaru City (65.7%). There were 30 patients (44.8%) who underwent microscopic examination, 12 patients (44.4%) who had a previous medical history of TB disease who had been informed finished taking medication by their doctors. Nine patients (33.3%) with a history of inadequate TB treatment. Three patients (11.1%) were confirmed as a treatment failure. Three patients (11.1%) were primary TB and confirmed the result of laboratory tests for resistance to anti-TB drugs. MDR TB patients who smoke were nine patients (33.3%), and DM patients were two people (7.4%). So, information about the characteristics of Multi-Drug Resistance Tuberculosis is needed, and it is hoped that appropriate treatment can be given

High Incidence of Psychiatric Disorders Associated with Cycloserine Treatment of Multidrug-Resistant Tuberculosis Patients: A Cohort Study in Beijing, China.

ObjectiveCycloserine (CS) is a group B anti-tuberculosis (TB) drug endorsed by the World Health Organization (WHO) for the treatment of drug-resistant (DR)-TB. Despite CS widespread acceptance and known efficacy, the high potential of drug-associated psychiatric disorders is a major concern to multidrug-resistant (MDR)-TB patients. In this study, we investigated CS-associated psychiatric disorders in a cohort of MDR-TB patients in Beijing, China. Our aim was to determine psychiatric disorder prevalence rates and associated risk factors in this population.MethodsThis MDR-TB cohort study was conducted at Beijing Chest Hospital between February 2018 and February 2021. All patients received individualized treatment regimens that included CS at some point during the full treatment course. Patient psychological status was assessed using the Symptom Checklist (SCL-90) questionnaire during the post-treatment follow-up period.ResultsTwo hundred and thirty-seven MDR-TB patients were included in the final analysis. Overall, psychiatric disorders were recorded in 22 (9.28%) of the 237 patients in our cohort, with severity grades of 1 or 2 observed for the majority (8.44%) of psychiatric adverse events. As compared to results obtained for control group patients who were ≥40 years of age, patients who were <40 years of age (77.3%, 17/22) were more likely to experience psychiatric disorders [adjusted odds ratio (aOR) = 3.060; 95% CI (1.060–8.828)]. Additionally, patients with body mass index (BMI)s of <18.5 kg/m2 [aOR = 3.824; 95% CI (1.502–9.739)] had significantly higher odds of being afflicted with psychiatric disorders as compared with patients with BMIs that were ≥18.5 kg/m2.ConclusionOur results demonstrated that approximately one-tenth of Chinese MDR-TB patients experienced psychiatric disorders during CS treatment, with the majority of adverse events of moderate severity. In addition, low BMI and age <40 years were identified as independent risk factors for psychiatric disorders in MDR-TB patients receiving CS therapy.

Efficacy of using bedaquiline in treatment of tuberculosis patients with multiple and extensive drug resistance

The objective: to compare treatment efficacy of pulmonary tuberculosis patients with multiple (MDR) and extensive drug resistance (XDR) using a standard chemotherapy regimen and the regimen containing bedaquiline.Subjects and Methods. A retrospective study was conducted to analyze treatment outcomes in 219 patients with pulmonary tuberculosis and MDR/XDR of Mycobacterium tuberculosis (MTB) aged 18-75 years old who were treated in in-patient and out-patient facilities of St. Petersburg from 2016 to 2019. Treatment outcomes were analyzed by subgroups formed taking into account resistance patterns and addition of bedaquiline to the treatment regimens: Ia – n = 94 (MDR TB; Bq-) and IIa ‒ n = 80 (XDR TB; Bq-); Ib ‒ n = 22 (MDR TB; Bq+) and IIb ‒ n = 23 (XDR TB; Bq+). Clinical and laboratory parameters of patients, the severity of comorbidity were assessed before the start of treatment, after 3, 6, 12-14 and 18-24 months of therapy, as well as after therapy completion and during the follow-up period. Statistical analysis was carried out using Statistica 10.0 and methods of parametric and nonparametric statistics and the SPSS 16.0 software, where p ≤ 0.05 was considered significant.Results. XDR TB patients in Subgroup IIb were significantly more likely to have a high level of comorbidity according to Charlson index (from 5 to 6 points) – in 34.7% of cases versus 5.0% in Subgroup IIa. At all stages of treatment in MDR TB patients with Bq+ (Ib), sputum conversion was recorded significantly more often versus patients of Subgroup Ia with Bq- when examined at all stages, with maximum effectiveness achieved by 18-24 months of treatment (90.9%). Treatment efficacy of XDR TB patients (IIb, Bq+) was also significantly higher versus treatment regimen containing no bedaquiline (60.8% (IIb, Bq+) versus 25.0% (IIa, Bq-), χ2 = 4.61, p &lt; 0.05).Conclusions. Achieved high efficacy of therapy in Subgroups Ib and IIb containing Bq provided a positive impact on treatment default rates, that were recorded in a low percentage of cases in those subgroups. An ineffective course of treatment in MDR TB patients treated with regimens containing no Bq was observed in 42.5% in Subgroup Ia, while this rate made only 0.09% in Subgroup Ib. Treatment effectiveness was the highest in XDR TB patients of Subgroup IIb when Bq was added to the treatment regimen.

RESISTENSI OBAT PADA PASIEN TUBERKULOSIS PARU DI PUSKESMAS BATU HORPAK KABUPATEN TAPANULI SELATAN

Tuberculosis (TB) is an infectious disease with a very high prevalence in several countries in the world. Inadequate TB treatment can cause tuberculosis bacterial resistance to OAT (Anti-Tuberculosis Medicine). The emergence ofresistance M. tuberculosis can be in the form of single drug resistance (DR-TB) or a number or all of the first-line OAT (Multidrug Resistance Tuberculosis). The purpose of this study was to determine drug resistance factors which are influenced by patient habits, medical history, drugs, and health services. This type of research is qualitative research with a case study approach method. There were 6 informants in this study who were two MDR-TB patients, two patient personal monitors, a doctor, and the person in charge of the tuberculosis section. The results showed that the patient had a smoking habit and had a previous history of tuberculosis. In terms of treatment, patients do not routinely take medicines while in health services, the puskesmas have run them well so that there are no mistakes in management. The conclusion of this study is that smoking habits, previous history of tuberculosis disease, and not routine treatment are factors that greatly influence the occurrence of resistance

BLOCKING PD-1 RESCUES PROTECTIVE T CELL RESPONSE TO FACILITATE BACILLARY CLEARANCE AND MODULATION OF THE EFFLUX PUMP EXPRESSION OF MYCOBACTERIUM TB

TYPE: Late Breaking Abstract TOPIC: Chest Infections PURPOSE: Previously, we have shown the critical role of regulatory Treg cells and PD-1 pathway in causing suppressed state of Tcell response against Mycobacterium tuberculosis among TB patient. In this study, we attempted to understand the status of host immune response among the MDR and Drug Sensitive TB patients. We also checked the contribution of PD-1 pathway on poly-functional Tcells,critical for protective immunity in TB. METHODS: For immune response profile and invitro experiments, polychromatic flowcytometry based immunological assays were performed.PD1 blocking experiments were performed in mice infected with Mtb. RESULTS: We observed rescue of PFTS in TB patients by blocking PD-1.We also observed that PFTs (IFN-γ+ TNF-α+) undergo apoptosis in TB patients due to higher expression of PD-1.Blocking PD-1 pathway in vivo among mice infected with Mtb, demonstrated restoration of PFTs with enhanced reduction of bacillary load. We observed increase in the frequency of Tregs whereas decrease in the PFTs response in Drug Resistant as compared to Drug Sensitive TB patients. Furthermore, we observed modulation of efflux pump of M.tb by pro-inflammatory (IFN-γ , TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β) in invitro MDM model. CONCLUSIONS: Our results demonstrate elicitation of weaker effector T cell response in DR TB compared to DS TB patients.Our results showed that rescuing appropriate immune response improves the efficacy of anti-tubercular therapy in TB. CLINICAL IMPLICATIONS: Our findings suggest critical role of PD-1 in suppressing the protective immune response in TB. Rescuing PFTs by blocking PD-1 pathway may offer a novel strategy for adjunct immunotherapy in TB. DISCLOSURE: Nothing to declare. KEYWORD: Tuberculosis PD1 Regulatory T cells Polyfunctional T cells

Search for ways to improve the effectiveness of treatment of pulmonary tuberculosis patients with multiple resistance of mycobacterium tuberculosis to anti-tuberculosis drugs

Aim. To conduct a comparative study of the effectiveness of treatment of MDR-TB patients by using short-term and individual chemotherapy regimens and including the drug Cholecalciferol in the treatment complex.Material and methods. The group of MDR-TB patients with a short-term treatment regimen included 40 patients, and 40 patients were included in the group of MDR-TB patients with an individual treatment regimen. Both observation groups were divided into two subgroups of patients with MDR-TB of the lungs (20 people from each group). In one group treatment included Cholecalciferol 300,000 U intramuscularly weekly (6-8 times in total) in the complex of the above treatment; comparison groups: patients with MDR-TB of the lungs (20 people from each group) received a complex of the above chemotherapy without the drug Cholecalciferol.Results. In the group of patients with the inclusion of Cholecalciferol in a short-term treatment regimen, a favorable treatment outcome was noted in 100% of cases, while in the group of patients without Cholicalciferol - in 80% of cases. With an individual treatment regimen in the group of patients with the inclusion of Cholecalciferol, conversion by sputum culture also occurred in 100% of cases, while in the group of patients without Cholicalciferol - in 70% of patients.Conclusion. Thus, the introduction of a new short-term chemotherapy regimen for MDR-TB patients has increased the effectiveness of their treatment. In two subgroups of MDR-TB patients with different chemotherapy regimens, who received injections of Cholecalciferol in the chemotherapy treatment plan, the effectiveness of treatment based on the results of the timing of the development of conversion by sputum culture was assessed as significantly higher than in the subgroups that did not receive vitamin D3.

Whole genome sequencing-based drug resistance predictions of multidrug-resistant Mycobacterium tuberculosis isolates from Tanzania.

BackgroundRifampicin- or multidrug-resistant (RR/MDR) Mycobacterium tuberculosis complex (MTBC) strains account for considerable morbidity and mortality globally. WGS-based prediction of drug resistance may guide clinical decisions, especially for the design of RR/MDR-TB therapies.MethodsWe compared WGS-based drug resistance-predictive mutations for 42 MTBC isolates from MDR-TB patients in Tanzania with the MICs of 14 antibiotics measured in the Sensititre™ MycoTB assay. An isolate was phenotypically categorized as resistant if it had an MIC above the epidemiological-cut-off (ECOFF) value, or as susceptible if it had an MIC below or equal to the ECOFF.ResultsOverall, genotypically non-wild-type MTBC isolates with high-level resistance mutations (gNWT-R) correlated with isolates with MIC values above the ECOFF. For instance, the median MIC value (mg/L) for rifampicin-gNWT-R strains was >4.0 (IQR 4.0–4.0) compared with 0.5 (IQR 0.38–0.50) in genotypically wild-type (gWT-S, P < 0.001); isoniazid-gNWT-R >4.0 (IQR 2.0–4.0) compared with 0.25 (IQR 0.12–1.00) among gWT-S (P = 0.001); ethionamide-gNWT-R 15.0 (IQR 10.0–20.0) compared with 2.50 (IQR; 2.50–5.00) among gWT-S (P < 0.001). WGS correctly predicted resistance in 95% (36/38) and 100% (38/38) of the rifampicin-resistant isolates with ECOFFs >0.5 and >0.125 mg/L, respectively. No known resistance-conferring mutations were present in genes associated with resistance to fluoroquinolones, aminoglycosides, capreomycin, bedaquiline, delamanid, linezolid, clofazimine, cycloserine, or p-amino salicylic acid.ConclusionsWGS-based drug resistance prediction worked well to rule-in phenotypic drug resistance and the absence of second-line drug resistance-mediating mutations has the potential to guide the design of RR/MDR-TB regimens in the future.

Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis

IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. MethodsWe reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. ResultsAfter reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). ConclusionsIn MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.

CHALLENGES IN INITIATION OF TREATMENT OF MULTI DRUG RESISTANT-TB PATIENTS: A HOSPITAL BASED CROSS SECTIONAL STUDY IN JHARKHAND.

BACKGROUND: Multi-drug resistant tuberculosis has become major public health problem and obstacle to effective control of tuberculosis. Over a period of time, there are several landmark achievements including policy and system preparedness for universal access to TB care including mandatory notication of TB cases, development of standard for TB care in India, comprehensive real time TB information management system-NIKSHAY, use of rapid molecular diagnostics, successful innovations in private sector engagement for TB care-Universal access to TB care. Objective was to nd out the challenges in initiation of treatment of Multi Drug Resistant-TB patients get admitted in ITKI Sanatorium Ranchi Jharkhand. METHODS: It was a hospital based cross sectional study carried out from August 2016 to Nov.2018 on Multi drug resistant tuberculosis patients admitted in MDR-TB centre Itki Sanatorium Ranchi after approved from institutional ethics committee. Total study subjects included in study was 64. RESULTS: Most of the study subjects 58 (90.6%) did not know about the MDR-TB. Most of the study subjects 40 (62.5%) had been given reports of CB-NAAT test on same day followed by study subjects 24 (37.5%) on alternate day. No one study subjects 64 (100%) had been given any type of incentive for travelling to pretreatment evaluation centre. In above table, most of the patients 51 (79.7%) had made payment for investigations at district hospital/ SDH level followed by 13 (20.3%) who were free of any expenditure for investigations. Most of the study subjects 60 (93.7%) were not visited by any health staff between nal diagnosis of MDR-TB and initiation of treatment for MDR-TB followed by subjects 4 (6.3%) who were being visited by health staff. Most of the study subjects 48 (75%) were unaware about the NIKSHAY POSHAN SCHEME for MDR-TB patients followed by subjects 16 (25%) who knew about the NIKSHAY POSHAN SCHEME for MDR-TB patients by means of various medium.

Pattern of resistance to second line anti-tuberculosis drugs and associated risk factors among multidrug-resistant patients of pulmonary tuberculosis from Agra region of Uttar Pradesh, North India

Present study was aimed to determine the status of second-line anti-TB drug resistance and risk factorsfor extensively drug-resistance (XDR)-tuberculosis among multi-drug resistant (MDR)-tuberculosis patients from Agra region of Uttar Pradesh, North India.A total of 279 MDR-Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients of Agra region of Uttar Pradesh were analyzed for the resistance to second-line anti-TB drugs (SLDs). The demographic, behavioral, clinical and social information was compared with the results of drug susceptibility testing and analyzed statistically. Out of 279 MDR-isolates, 195 (69.89%) isolates were found resistant to at least one of the SLDs. The rates of general resistance to each of the drugs were as follows: kanamycin (42.29%), amikacin (17.92%), levofloxacin (40.14%) and ofloxacin (51.97%). Among the MDR-TB isolates, 53.76, 43.01 and 26.88% isolates were resistant to fluoroquinolone, second line injectable drugs and XDR, respectively. Among the demographic/ clinical variables, occupation, gender and number of family members were associated with the development of XDR-TB in MDR-TB patients of Agra region of Uttar Pradesh(P value: &lt;0.05).Present study has provided baseline information about the risk factors associated with SLDs resistance and XDRamong MDR-TB patients which can be useful to strengthen the implementation of targeted interventions in order to minimize the cases of drug resistance tuberculosis in Uttar Pradesh, North India.

Safety and Efficacy of Multiple Drug Resistant Tuberculosis Treatment in Patients with Different HIV Statuses

The objective: to analyze and compare frequency and variety of adverse events (AEs) and their impact on outcomes of tuberculosis therapy when treating patients with multiple drug resistant tuberculosis (MDR TB) and different HIV statuses.Subjects and Methods: retrospective observational case-control study of patients registered for treatment with the 4th regimen of chemotherapy for tuberculosis in the city of Vladimir and Vladimir Region in 2014-2016.Results. The proportion of patients who reported any AE during the MDR TB treatment was similar among HIV positive and HIV negative patients and made 85.5%. In patients with concurrent HIV infection and MDR TB, hematopoietic AEs such as anemia, thrombocytopenia were more frequent, while neutropenia was significantly more frequent when comparing groups by the cumulative event probability method. Elevated eosinophil level during treatment was more typical of MDR TB patients. Treatment outcomes in the group of patients with HIV and MDR TB were statistically significantly worse due to the higher frequency of fatal outcomes. At the same time, there was no correlation of AE with unfavorable treatment outcomes. The early initiation of combination therapy with thorough monitoring of hematologic parameters in patients with HIV and MDR TB was safe and effective.

Multi-drug-resistant tuberculosis clusters in Mpumalanga province, South Africa, 2013-2016: A spatial analysis.

To identify spatial clusters with unusually high levels of MDR-TB, which are highly unlikely to have arisen by chance in Mpumalanga Province, South Africa. Home addresses of all MDR-TB patients were collected from four MDR-TB facilities from 2013 to 2016. We mapped all addresses, linking them to the nearest ward with population estimates. A spatial analysis was conducted using kernel density in ArcGIS to estimate and map the distribution of the disease and used Gertis-Ord Gi to test for significant clustering. A total of 4065MDR-TB patients were mapped. Ten significant clusters (p-value <0.05) were found across the province in six sub-districts: Mbombela, Nkomazi, Emalahleni, Govan Mbeki, Lekwa and Mkhondo. Mbombela has the highest number of significant clusters. The central region did not have any MDR-TB clusters. There is clear evidence of MDR-TB clustering in Mpumalanga. This calls for concentrated TB prevention efforts and proper allocation of resources. Further investigations are needed to identify MDR-TB predictors.

Correlation between N-Acetyltransferase 2 (NAT2) Polymorphism Genotype with Plasma Isoniazid (INH) Concentration in MDR TB Patients Receiving Short Regimen in West Sumatera

Background: Isoniazid (INH) is one of the most potent TB drug. High dose INH is used in short regimen MDR TB drugs. The genetic polymorphism of NAT2 affects the acetylation status. Awareness of the patients’ acetylator status is important to determine the risk of toxicity, treatment failure and drug resistance. The aim of this study was to demonstrate NAT2 genotype association with INH plasma concentration after 2 hours of oral INH therapy. Methods: This was a cross sectional study of MDR TB patients who received short term combination therapy at RSUP Dr. M.Djamil Padang, Achmad Muchtar Hospital Bukittinggiand West Sumatra Pulmonary Hospital from September 2019 to February 2020. Patients were examined for NAT2 genotype and plasma INH concentration. The results of the plasma INH concentrations obtained were evaluated based on the NAT2 acetylator phenotype group.Results: The majority of the subjects weremen (62.5%), aged 40-64 years (50%), had the most common comorbid of diabetes mellitus (31.25%), were normoweight (75%) and had negative HIV status (93.8%). A total of 7 alleles consisting of 7 SNPs and 7 variations of the NAT2 genotype were found in MDR TB patients who received short-term therapy. The NAT2*12A alleles (56.25%) was the most common allele and was a fast acetylator. Based on the bimodal distribution, the median concentration of INH in the fast and slow acetylator were 1.25 µg/ml and 5.24 µg/ml, respectively. The median values of INH concentration based on the trimodal distribution for fast, intermediate, and slow acetylators were 1.25 µg/ml, 2.17 µg/ml and 5.24 µg/ml. Conclusion: There were no correlations between the type of NAT2 acetylator phenotype and plasma INH concentrations.